New developments in cardiovascular surgery continue to advance the frontiers of technical possiblities for correction of valvular and circulatory abnormalities. However, clinical barriers to the application of corrective surgical techniques remain, especially problems such as increased pulmonary resistance and altered vascular permeability following prolonged cardiac bypass pumping or use of other circulatory assist devices. There is growing experimental evidence that leukocyte damage produced by mechanical shear stress and/or exposure to foreign material is a major cause of the "shock-lung" reaction. The present proposal will study the effects of precisely defined in vitro shear stress on leukocyte morphology and function. Experiments will be conducted to determine the threshold for damage to membrane and cytoskeletal functions. Pharmacologic agents which affect microtubule and microfilament assembly will be utilized as probes to evaluate the role of the cytoskeleton in preserving leukocyte integrity. Platelet active drugs will also be evaluated for protective effects with leukocytes subjected to shear stress. The long-term objective of this research is to determine the levels of shear stress exposure which will damage leukocytes, and to determine whether pharmacologic agents can increase leukocyte resistence to damage. These data would be important as criteria for designing artificial circulatory assist devices or other apparatus in which blood is pumped or artificial materials are introduced into the circulatory system.